The hepatocellular vitamin D receptor regulates liver regeneration after partial hepatectomy

in intact tissues in vivo.Here, we are interested in characterizing and understanding the physiological role of hepatic SLC25A51.Method: We used AAV vectors expressing Slc25a51 or shRNA targeting under the control of the TBG promoter to overexpress or knock down Slc25a51, respectively, in the livers of mice.Results: Preliminary data show that the Slc25a51 knockdown mice have significantly higher fasting blood glucose and glucose intolerance, whereas overexpression has no effect.In contrast, overexpression lowers glucose in a pyruvate tolerance test whereas knockdown has no effect.As expected, mitochondrial NAD+ and NADH content and redox ratio are significantly higher in the over-expressors without a major change in total tissue NAD.Overexpression of SLC25A51 increased mitochondrial respiration and increased the rate of NAD+ uptake into isolated mitochondria.Conversely, loss of SLC25A51 impaired mitochondrial function.In addition, overexpression of SLC25A51 enhanced liver regeneration, significantly improved mitochondrial respiration and increased NAD+ uptake in post regenerative isolated mitochondria.Conclusion: So far, our data suggest a direct enhancement of mitochondrial redox metabolism as the mechanism mediating improved regeneration in the over-expressors.Thus, the role of SLC25A51 appears to be conserved in vivo and impacts liver regeneration.